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T Osuga

Publications and source records attributed to T Osuga.

At least 55 records · Page 3Linked to original sources
PubMed1994

Autofluorescence in onset of gastric mucosal injury induced by hemorrhagic shock in rats.

In an attempt to clarify whether gastric mucosal autofluorescence can help us to recognize gastric lesions at the onset of their formation, we investigated the fluorescence generated from the gastric mucosa of rats under ischemia-reperfusion stress. Red-colored fluorescence appeared and began to increase within 5 min after reperfusion. Such an increase in fluorescence did not occur in the gastric mucosa under prolonged ischemia without reperfusion. The epifluorescence microscopy of mucosal cryosections revealed that fluorescence was present even when only superficial mucosal damage occurred. Spectrofluorometric and high-performance liquid chromatographic analysis of the fluorescent mucosa extract identified the fluorescent substances as porphyrins. These findings suggested that fluorescent porphyrins are generated in the mucosal layer during the introductory phase of mucosal lesion formation induced by ischemia-reperfusion stress.

Animals↗
PubMed1994

A new, effective, and safe therapeutic option using proton irradiation for hepatocellular carcinoma.

BACKGROUND/AIMS: Conventional radiation is almost useless for hepatocellular carcinoma (HCC) because of the severe adverse effects of the irradiation to the accompanying liver cirrhosis. In contrast, the proton beam has Bragg peak, which limits distribution of the beam. The aim of this study was to prove the usefulness of proton irradiation for HCC. METHODS: The proton irradiation was performed in 32 nodular lesions in 24 patients with HCC who had unresectable tumors or serious complications; the proton irradiation was performed either as monotherapy (15 lesions) or as combination therapy to insufficient Lipiodol-targeted chemotherapy (Kodama Co. Ltd., Tokyo, Japan) (17 lesions). The energy was 250 MeV, and 50-87 Gy (76.5 +/- 9.5, mean +/- SD) in total was irradiated for a time period of 17-69 days. RESULTS: After 1 year, size reduction was seen in 12 out of 13 lesions (92%) in the monotherapy group and 9 out of 9 lesions (100%) in the combination therapy group; after 2 years, size reduction was seen 4 out of 5 lesions (80%) in the monotherapy group and 5 out of 5 lesions (100%) in the combination therapy group. Local tumor control has being assured for 2 years of the observation, which is continuing for another 2 years. None of the patients have experienced any serious adverse effects. CONCLUSIONS: These results show that proton irradiation is a new, safe, and effective therapeutic option in cases of HCC, even in patients with unresectable tumors or those with serious complications.

Aged↗
PubMed1994

Biochemical and histological changes after more than four years of treatment of ursodeoxycholic acid in primary biliary cirrhosis.

We report on three patients with symptomatic, anicteric, and noncirrhotic primary biliary cirrhosis (Ludwig histological stage III at first liver biopsy) who were treated orally with 600 mg/day of ursodeoxycholic acid (UDCA) for more than 4 years. Follow-up liver biopsy was performed twice (at 1-3 and 4-6 years) during treatment. In all cases, during the whole period of up to 4-6 years of UDCA treatment, transaminase, alkaline phosphatase, and gamma-glutamyltranspeptidase levels improved, remaining at subnormal levels compared with pretreatment levels. Moreover, histological stage did not change throughout the UDCA treatment of up to 6 years. The second liver biopsy (at 1-3 years) revealed decreased lymphocytic infiltration in all cases, and bridging fibrosis was decreased in two cases. However, in the third biopsy at 4-6 years, portal inflammation was increased in one case without fibrotic progression; in the other two cases, bridging fibrosis was slightly worsened without portal inflammatory progression. In summary, these three cases show that liver histology was found to be improved, as were blood chemistry and pruritus, during short-term UDCA treatment, but histology results were slightly worse after long-term treatment despite the sustained improvement in biochemistry and pruritus.

Adult↗
PubMed1994

Induction of autoimmune disease by graft-versus-host reaction across MHC class II difference: modification of the lesions in IL-6 transgenic mice.

We examined the effect of IL-6 on the development of autoimmune diseases (primary biliary cirrhosis, Sjögren's syndrome) employing murine graft-versus-host reaction (GVHR) model with MHC class II disparity. For this purpose, we used IL-6 transgenic (B6.6) mice in which a high level of IL-6 was detected. C57Bl/6 (B6) spleen T cells were injected into B6.6 mated with B6.C-H-2bm12 (bm12) mutant mice ((bm12 x B6.6)F1) and GVHR with MHC class II disparity was induced. The transgenic hybrid mice with GVHR showed a larger spleen index and contained a higher serum level of IL-6 than those without GVHR. Autoimmune-like lesions in transgenic recipients became weakened compared with those in non-transgenic (bm12 x B6)F1 recipients. In contrast, levels of antimitochondrial antibodies in (bm12 x B6.6)F1 GVHR group were significantly higher than that of (bm12 x B6)F1 GVHR group. These results indicate that IL-6 excessively produced in vivo might regulate the progression of autoimmune diseases.

Animals↗
PubMed1994

[Anesthetic management of a patient with Freeman-Sheldon syndrome].

The Freeman-Sheldon syndrome is a rare congenital myopathy and dysplasia that results in deformity of the face, hands, and feet. We describe here some problems in general anesthesia from the anesthetic management point of view. An 8-year-old girl with Freeman-Sheldon syndrome underwent surgery under general anesthesia for the correction of lip deformity and microstomia. Patients with this syndrome may present anesthetic problems involving difficulties in endotracheal intubation due to microstomia, micrognathia and neck rigidity, as well as postoperative respiratory complications and problems that relate to myogenetic morphology and myofunctional abnormalities. Preoperatively, we analyzed X-ray cephalograms to evaluate the difficulty of endotracheal intubation. Fiberscopic endotracheal intubation was performed; the time required was 55 minutes. On recovery from anesthesia and after becoming fully responsive, she was extubated in the operating room without any complications. Postoperative recovery was uneventful. Patients with Freeman-Sheldon syndrome should be managed by good preanesthetic preparation, and attention should be paid to postoperative respiratory complications due to the use of muscle relaxants and to securing intravenous access.

Abnormalities, Multiple↗
PubMed1994

Proton beam therapy for patients with esophageal carcinoma.

Fifteen patients with esophageal carcinoma (superficial, six cases; advanced, nine cases) were treated with 250 MeV proton beam irradiation with or without external x-ray irradiation (12 MV linear accelerator) from October, 1985, to May, 1991. Eleven patients were initially treated with x-ray at doses of 16.2-50.4 (mean 42.5) Gy, followed by proton beam at doses of 30.0-52.9 (mean 37.6) Gy. The other four patients were treated with proton beams alone at total doses of 75.0-88.5 (mean 81.4) Gy. The mean total dose for the 15 patients was 80.4 Gy. As a result, the primary tumor lesions of all 15 patients disappeared and complete responses were obtained. Approximately four to five months later, nine of the 15 patients developed esophageal ulcer formations at the circumferences of their primary lesions. The ulcerations were healed, however, by conservative management. There was no evidence of local recurrence throughout the observations on six cases of superficial carcinoma. Among nine advanced carcinoma patients, three relapsed into esophageal carcinoma. Recurrences were observed eight, 16 and 44 months, respectively, after the treatment. Ten of the 15 patients died, but eight died of other diseases. Three of four cases at autopsy did not show any cancer cells in irradiated primary lesions. Four of the 15 patients lived for over five years. The results suggest that a high dose of irradiation delivered by a well-defined proton field could result in improved local control and long-term survival in esophageal carcinoma without undue risk of injury to primary and adjacent organs.

Aged↗
PubMed1993

Simultaneous determination of mevalonate and 7 alpha-hydroxycholesterol in human plasma by gas chromatography-mass spectrometry as indices of cholesterol and bile acid biosynthesis.

A very sensitive and specific method for the simultaneous determination of mevalonate and 7 alpha-hydroxycholesterol in human plasma is described. The assay is based on isotope dilution mass spectrometry: the extracts from plasma were treated with benzylamine followed by dimethylethylsilylimidazole, then the resulting dimethylethylsilyl ether derivatives of mevalonylbenzylamide and 7 alpha-hydroxycholesterol were determined by gas chromatography-mass spectrometry using high-resolution selected-ion monitoring. Simple regression analysis revealed significant correlations between the plasma level of mevalonate and the hepatic activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 1.1.1.34) (r = 0.83, P < 0.01) and between the plasma level of free 7 alpha-hydroxycholesterol and the hepatic activity of cholesterol 7 alpha-hydroxylase (EC 1.14.13.7) (r = 0.76, P < 0.05).

Adult↗
PubMed1993

Pharmacokinetic profiles of glycyrrhizin in patients with chronic hepatitis.

The pharmacokinetics of glycyrrhizin (G) in eight patients with chronic hepatitis receiving chronically i.v. administration of 120 mg dose of G was investigated. The plasma concentration of G in the patients after dosing declined in a monophasic manner. However, the pharmacokinetic profiles varied among patients. The mean elimination half-life (t1/2) and the total body clearance (CLtot) were 6.0 h (range 4.3-10.7 h) and 7.9 ml h-1 kg-1 (4.5-12.7 ml h-1 kg-1), respectively. The variation of the CLtot for G was closely related to that of aspartate aminotransferase (r = -0.739, p < 0.05) and alanine aminotransferase (r = -0.783, p < 0.05) activities in the plasma.

Adult↗
PubMed1993

Alterations of bile acid composition in gallstones, bile, and liver of patients with hepatolithiasis, and their etiological significance.

A detailed comparison was made of the bile acid composition in gallstones (brown pigment stones) and paired bile and liver from both affected and unaffected lobes by gallstones, which were taken at operation from 16 patients with hepatolithiasis, with the aim of elucidating whether stone formation is derived from possible local disturbances limited to intrahepatic bile ducts. Brown pigment stones in the intrahepatic bile ducts, most of which were accompanied by bile with high cholesterol saturation, had significantly more cholesterol, and less calcium bilirubinate and bile acid than those found in the extrahepatic bile ducts. Intrahepatic gallstones had significantly lower amounts of secondary and unconjugated bile acids, the bile acids modified by bacterial intervention, than extrahepatic stones. Bile specimens from both affected and unaffected lobes showed significantly increased molar percentages of cholesterol and decreased percentages of bile acids than bile from controls. In contrast, liver specimens from both lobes showed significantly higher concentrations of total bile acids. Secondary bile acids were present in a much lower proportion in bile and liver from both lobes than in bile and liver from controls. On the other hand, unconjugated bile acids were present in a much higher proportion in bile and liver from patients and only in negligible amounts in bile from controls. Furthermore, the plasma levels of mevalonate and those of 7 alpha-hydroxy-4-cholestene-3-one were found to be significantly higher and lower in patients than in controls, respectively, indicating that in hepatolithiasis cholesterol synthesis might increase and bile acid synthesis might decrease in the liver. These findings suggested that alterations of bile acid composition in gallstones, bile, and liver of patients with hepatolithiasis may be attributed to not only secondary changes resulting from local disturbances limited to intrahepatic bile ducts but also possible primary alterations of hepatocyte metabolism, such as bile acid conjugation and primary defects in cholesterol and bile acid synthesis.

Bile↗
PubMed1993

High prevalence of hepatitis B and C viral markers in Japanese patients with hepatocellular carcinoma.

In order to assess the etiologic role of hepatitis C virus (HCV) as well as hepatitis B virus (HBV) in the etiology of HCC, we compared the prevalence of HCV-related antibodies (anti-C100-3, anti-CP9, anti-CP10) and HBV-related markers (HBsAg, anti-HBs, anti-HBc) in sera of patients with liver cirrhosis (LC) with (n = 62) and without (n = 54) hepatocellular carcinoma (HCC). In HBsAg-negative cases, at least one HCV-related marker (including HCV RNA) was detected in 92.3% (48/52) of HCC cases and in all of the 44 LC cases without HCC, with no significant difference between these two groups. In HBsAg-positive cases, the prevalence of either one of these HCV-related markers was 40.0% (4/10) both in patients with and without HCC, and there was no significant difference between these two groups. Moreover, in HBsAg-negative cases and 11 cases of positive HCV-related markers, the prevalence of anti-HBs and/or anti-HBc was significantly higher in LC patients with HCC (85.4%) than those without HCC (43.2%, P < 0.001). These results show a high prevalence of hepatitis B and C viral markers in Japanese patients with HCC and further indicate that previous HBV infection is a risk factor in the occurrence of HCC in HBsAg-negative LC and LC with positive HCV-related markers.

Carcinoma, Hepatocellular↗
PubMed1993

Hepatic cholesterol and bile acid synthesis in Japanese patients with cholesterol gallstones.

In Japan the composition of gallstones is changing rapidly from the once-predominant brown-pigment stones to cholesterol ones. The present work was undertaken to clarify the mechanism of cholesterol supersaturated bile production in Japanese patients with cholesterol gallstones. In 26 non-obese and normolipidemic patients (11 with cholesterol gallstones, 8 with black- or brown-pigment gallstones, 7 without gallstones) a liver biopsy and hepatic bile were surgically obtained under standardized conditions. The cholesterol saturation of hepatic bile was significantly higher in cholesterol gallstone patients than in gallstone-free controls (195 +/- 10 vs. 146 +/- 8%, respectively; P < 0.01). The microsomal activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for cholesterol synthesis, cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme for bile acid synthesis, and 7 alpha-hydroxy-4-cholesten-3-one 12 alpha-hydroxylase (12 alpha-hydroxylase), the rate-limiting enzyme for cholic acid synthesis, were assayed simultaneously in the same subjects. There were positive correlations between HMG-CoA reductase and cholesterol 7 alpha-hydroxylase activities (Rs = 0.62, P < 0.005), and between cholesterol 7 alpha-hydroxylase and 12 alpha-hydroxylase activities (Rs = 0.44, P < 0.05) in all subjects, irrespective of the existence of gallstones. The activities of the three rate-limiting enzymes did not differ significantly among the three groups (cholesterol stone, pigment stone and stone-free). In conclusion, the cholesterol supersaturation of hepatic bile in nonobese and normolipidemic Japanese patients with cholesterol gallstones does not result from an increased hepatic cholesterol synthesis or a decreased bile acid synthesis.

Bile Acids and Salts↗
PubMed1993

Endothelin-1-induced gastric ulcer is attenuated by cetraxate.

We investigated the effect of the anti-ulcer drug cetraxate on the development of the gastric ulcer induced by the submucosal injection of endothelin-1 in the rat gastric body, and its effects on gastric mucosal hemodynamics and tissue oxygenation by Laser doppler flowmetry and tissue spectrophotometry. Endothelin-1 induced gastric ulcer (ulcer length: 11.85 +/- 0.89 mm, mean +/- SEM, n = 4) which was strongly attenuated by cetraxate (ulcer length: 3.27 +/- 0.3 mm, mean +/- SEM, n = 8, p < 0.0001). Cetraxate maintained also tissue oxygenation without causing any significant effect on the endothelin-1-induced changes in gastric mucosal blood flow and volume. These results show that cetraxate exerts its cytoprotective action partly by maintaining mucosal oxygenation.

Animals↗
PubMed1993

Gastric ulcer induced by submucosal injection of ET-1: role of potent vasoconstriction and intraluminal acid.

To investigate whether submucosally applied endothelin-1 (ET-1) can induce gastric ulcer, ET-1 (62.5, 125, 250, and 500 pmol/kg) was injected in the submucosal layer of the rat gastric body. Twenty-four hours later, gastric ulcer (ulcer area: 10.31 +/- 5.13 mm2, mean +/- SE, at 500 pmol/kg, n = 8) was induced. The mucosal damage induced by the two highest doses was present even at 2 wk after their injection. Measurement of the mucosal blood flow at the injected area with three different methods (laser-Doppler flowmetry, hydrogen gas clearance, and reflectance spectrophotometry) revealed that injected ET-1 produced an extremely long-lasting vasoconstriction. Pretreatment with nicardipine, a Ca(2+)-channel blocker (1 mg/kg iv), significantly attenuated the ET-1-induced mucosal damage as well as the decrease in mucosal blood flow. Pretreatment with omeprazole (5-40 mumol/kg) also, significantly attenuated the ET-1-induced mucosal damage. Combined pretreatment with omeprazole (40 mumol/kg) and nicardipine almost abolished the ET-1-induced damage. The present study shows that a novel model for experimental ulcers can be induced by submucosal injection of ET-1.

Acids↗
PubMed1993

Superficial and protruding type of esophageal adenocarcinoma mucocellulare and muconodulare confined mostly to the lamina propria mucosa and partly in the submucosal layer.

We report a case with an adenocarcinoma mucocellulare and muconodulare of the esophagus which is limited to the lamina propria mucosa and the submucosal layer. The patient, a 74-year-old man had the chief complaints of hematemesis and melena. A superficial and protruding (0-I) type of lesion was found at the lower thoracic portion of the esophagus by X-ray and endoscopic examination. The surgically resected esophageal specimen showed 0-I and predominantly subepithelial (Sep) type. The tumor is presumed to have arisen from the cardiac glands in the lamina propria mucosa of the lowermost region of the esophagus.

Adenocarcinoma↗